The proposal represents a continuation of our research in the area of islet cell culture and transplantation. The work is intended to serve as a basis for the eventual application of islet cell transplantation in Type 1 diabetes. Experiments within the proposal are directed toward the investigation of developing alternate methods for the acquisition of islet tissue. In addition, experiments involve the investigation of a unique method for the production of non-immunogenic islets which can be transplanted without immunosuppression between animals disparate at the major histocompatibility locus. Further understanding of the mechanism by which altered immunogenicity is attained is pursued. Methods for selective cell culture in which cells necessary for immune recognition can be controlled in vitro, are being explored. An experimental model of Type 1 diabetes as well as chemical forms of Type 1 diabetes are being examined to assess the utility of the technologies developed in the reversal of these hyperglycemic-insulinopenic syndromes. The approach centers on the acquisition of morphological data, coupled with biochemical and physiological studies. Technicques of immunoassay, morphometric analysis at the ultrastructural and light microscopical level, immunocytochemistry, spectrophotometry, chromatography, enzymology, tissue culture, transplantation permit the correlation of morphological, biochemical and physiological parameters. Major questions remain as barriers to human islet cell transplantation. Can efficient methods be developed for the isolation and purification of human islets? Can methods be developed permitting the purification of islet endocrine grafts circumventing rejection without the need for patient immunosuppression? Will the etiology of Type 1 diabetes be reexpressed in the transplanted grafts, compromising their function? It is hoped that experiments in this proposal will provide basic research which may lead to the answers to some of these questions.